MiR-31 Ablates Expression Of The HIF Regulatory Factor FIH To Activate The HIF Pathway In Head And Neck Carcinoma.
Chung-Ji Liu, Meng-Miao Tsai, Pei-Shih Hung, S. Kao, T. Liu, K. Wu, S. Chiou, Shu-Chun Lin, K. Chang
Published 2010 · Medicine, Biology
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MicroRNAs (miRNA) are endogenously expressed noncoding RNAs with important biological and pathological functions that are yet to be fully defined. This study investigated alterations in miRNA expression in head and neck squamous cell carcinoma (HNSCC), the incidence of which is rising throughout the world. Initial screening and subsequent analysis identified a panel of aberrantly expressed miRNAs in HNSCC tissues, with miR-31 among the most markedly upregulated. Ectopic expression of miR-31 increased the oncogenic potential of HNSCC cells under normoxic conditions in cell culture or tumor xenografts. Conversely, blocking miR-31 expression reduced the growth of tumor xenografts. The in silico analysis suggested that miR-31 may target the 3' untranslated region (UTR) of factor-inhibiting hypoxia-inducible factor (FIH), a hypoxia-inducible factor (HIF) regulatory factor that inhibits the ability of HIF to act as a transcriptional regulator under normoxic conditions. In support of this likelihood, miR-31 expression repressed FIH expression and mutations within the predictive miR-31 target site in the FIH 3' UTR abrogated FIH repression. Furthermore, miR-31 expression increased HIF transactivation activity. We found that FIH suppressed oncogenic phenotypes under normoxic conditions and that this activity was abrogated by functional mutations. Lastly, increased miR-31 expression was correlated with decreased levels of FIH in tumor tissues. Our findings suggest that miR-31 contributes to the development of HNSCC by impeding FIH to activate HIF under normoxic conditions.
This paper references
Expression of prolyl-hydroxylases PHD-1, 2 and 3 and of the asparagine hydroxylase FIH in non-small cell lung cancer relates to an activated HIF pathway.
Alexandra Giatromanolaki (2008)
Cytoplasmic locationof factor-inhibiting hypoxia-inducible factor is associated with an enhanced hypoxic response and a shorter survival in invasive breast cancer
Evidence That Two Enzyme-derived Histidine Ligands Are Sufficient for Iron Binding and Catalysis by Factor Inhibiting HIF (FIH)*
K. Hewitson (2008)
Cancer Res Cancer Research
Identification of hypoxia-inducible factor-1 alpha as a novel target for miR-17-92 microRNA cluster.
Ayumu Taguchi (2008)
A microRNA expression signature of human solid tumors defines cancer gene targets
S. Volinia (2006)
American Association for Cancer cancerres.aacrjournals.org Downloaded from
MiRNA expression in urothelial carcinomas: important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31.
S. Veerla (2009)
Association between High miR-211 microRNA Expression and the Poor Prognosis of Oral Carcinoma
K-W Chang (2008)
Intracellular localisation of human HIF-1α hydroxylases: implications for oxygen sensing
E. Metzen (2003)
MicroRNAs and cancer.
T. Dalmay (2008)
Genetic analysis of the role of the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH) in regulating hypoxia-inducible factor (HIF) transcriptional target genes [corrected].
Ineke P. Stolze (2004)
Association of Expression Aberrances and Genetic Polymorphisms of Lysyl Oxidase with Areca-Associated Oral Tumorigenesis
T. Shieh (2007)
A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis
Scott Valastyan (2009)
Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue
Thian-Sze Wong (2008)
MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis.
L. Yan (2008)
A MicroRNA Signature of Hypoxia
R. Kulshreshtha (2006)
MicroRNA alterations in head and neck squamous cell carcinoma.
S. Chang (2008)
Identification of hypoxiainducible factor - 1 α as a novel target for miR1792 microRNA clus
A Taguchi (2007)
Areca-treated Fibroblasts Enhance Tumorigenesis of Oral Epithelial Cells
H-H Lu (2008)
Direct regulation of TWIST by HIF-1α promotes metastasis
M. Yang (2008)
Asparaginyl Hydroxylation of the Notch Ankyrin Repeat Domain by Factor Inhibiting Hypoxia-inducible Factor*
M. Coleman (2007)
MicroRNA-210 Modulates Endothelial Cell Response to Hypoxia and Inhibits the Receptor Tyrosine Kinase Ligand Ephrin-A3*
P. Fasanaro (2008)
Altered Expression of miR-21, miR-31, miR-143 and miR-145 Is Related to Clinicopathologic Features of Colorectal Cancer
O. Slaby (2007)
High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma
C. Hebert (2006)
Overexpression of the Oxygen Sensors PHD-1, PHD-2, PHD-3, and FIH Is Associated with Tumor Aggressiveness in Pancreatic Endocrine Tumors
A. Couvelard (2008)
Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues
E. Bandrés (2006)
Diagnostic and therapeutic evaluation of 111In-vinorelbine-liposomes in a human colorectal carcinoma HT-29/luc-bearing animal model.
T. Chow (2008)
MicroRNAs: Target Recognition and Regulatory Functions
D. Bartel (2009)
MicroRNA Expression Ratio Is Predictive of Head and Neck Squamous Cell Carcinoma
Michele Avissar (2009)
Frequent loss of chromosome 9p21-22 early in head and neck cancer progression.
P. van der Riet (1994)
MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1.
Q. W. Wong (2008)
Ripe areca nut extract induces G1 phase arrests and senescence-associated phenotypes in normal human oral keratinocyte.
S. Lu (2006)
Cytoplasmic location of factor-inhibiting hypoxia-inducible factor is associated with an enhanced hypoxic response and a shorter survival in invasive breast cancer
E. Tan (2007)
Posttranslational hydroxylation of ankyrin repeats in IκB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH)
M. Cockman (2006)
Array-comparative genomic hybridization to detect genomewide changes in microdissected primary and metastatic oral squamous cell carcinomas.
Chung-Ji Liu (2006)
Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway
C. Dann (2002)
The impact of O2 availability on human cancer
Jessica A. Bertout (2008)
Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells
H. Tazawa (2007)
MiR-21 Indicates Poor Prognosis in Tongue Squamous Cell Carcinomas as an Apoptosis Inhibitor
Jinsong Li (2009)
Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines.
F. Meng (2006)
The oxygen sensor factor-inhibiting hypoxia-inducible factor-1 controls expression of distinct genes through the bifunctional transcriptional character of hypoxia-inducible factor-1alpha.
F. Dayan (2006)
Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis.
Y. Chen (2007)
MicroRNAs and the hallmarks of cancer
T. Dalmay (2006)
This paper is referenced by
Induced miR‐31 by 5‐fluorouracil exposure contributes to the resistance in colorectal tumors
Y. Nakagawa (2019)
The cellular response to hypoxia: tuning the system with microRNAs.
Joseph Loscalzo (2010)
microRNA 31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway
Takashi Mitamura (2013)
Placental microRNA expression in pregnancies complicated by superimposed pre-eclampsia on chronic hypertension
Elena S. Vashukova (2016)
MicroRNA-31 targets FIH-1 to positively regulate corneal epithelial glycogen metabolism.
Han Peng (2012)
Lipopolysaccharide induces the migration of human dental pulp cells by up-regulating miR-146a.
Min-Ching Wang (2012)
Correlation between Biological Marker Expression and 18F-Fluorodeoxyglucose Uptake in Cervical Cancer Measured by Positron Emission Tomography
Sang Ick Park (2013)
Expression and Significance of Circulating MicroRNA-31 in Lung Cancer Patients
Hai-Jun Yan (2015)
miR-193b/365a cluster controls progression of epidermal squamous cell carcinoma.
Cécile Gastaldi (2014)
Passenger strand miRNA miR-31* regulates the phenotypes of oral cancer cells by targeting RhoA.
Kuo-Wei Chang (2013)
Integrated Genomic and Functional microRNA Analysis Identifies miR-30-5p as a Tumor Suppressor and Potential Therapeutic Nanomedicine in Head and Neck Cancer
Anthony D. Saleh (2019)
The asparaginyl hydroxylase factor-inhibiting HIF is essential for tumor growth through suppression of the p53–p21 axis
Jerry Pelletier (2012)
Up-regulation of HB-EGF by the COX-2/PGE2 signaling associates with the cisplatin resistance and tumor recurrence of advanced HNSCC.
Cheng-Chieh Yang (2016)
A Quest for miRNA Bio-Marker: A Track Back Approach from Gingivo Buccal Cancer to Two Different Types of Precancers
Navonil De Sarkar (2014)
Dynamic changes in the expression of MicroRNA‐31 during inflammatory bowel disease‐associated neoplastic transformation
Alexandru V. Olaru (2011)
Factor inhibiting HIF1α (FIH-1) functions as a tumor suppressor in human colorectal cancer by repressing HIF1α pathway
Tao Chen (2015)
Title Interactions between E-cadherin and microRNA deregulation inhead and neck cancers : The potential interplay
A Ten-microRNA Expression Signature Predicts Survival in Glioblastoma
Sujaya Srinivasan (2011)
miR-134 induces oncogenicity and metastasis in head and neck carcinoma through targeting WWOX gene.
Chung-Ji Liu (2014)
Micro RNA Molecules as Modulators of Treatment Resistance, Immune Checkpoints Controllers and Sensitive Biomarkers in Glioblastoma Multiforme
Marek Mazurek (2020)
Disease-Associated miRNA-mRNA Networks in Oral Lichen Planus
Volker Gassling (2013)
Dysregulation of miR-31 and miR-375 expression is associated with clinical outcomes in oral carcinoma.
Ming Yhong Siow (2014)
The Cancer Genome Atlas Analysis Predicts MicroRNA for Targeting Cancer Growth and Vascularization in Glioblastoma.
Hon-Kit Andus Wong (2015)
SATB1 and 2 in colorectal cancer.
Jason Brocato (2015)
Up-regulation of miR-187 modulates the advances of oral carcinoma by targeting BARX2 tumor suppressor
Shu-Chun Lin (2016)
A microRNA expression signature for the prognosis of oropharyngeal squamous cell carcinoma.
G. Gao (2013)
MicroRNAs and Tumor Vasculature Normalization: Impact on Anti-Tumor Immune Response
Agata Matejuk (2013)
RETRACTED ARTICLE: Low p21 level is necessary for the suppressive effects of micoRNA-31 on glioma cell migration and invasion
Jun Pan (2016)
Novel Regulators of Pancreatic Cancer Cell Growth and Mobility
Eeva Laurila (2012)
MicroRNA-215-5p Treatment Suppresses Mesothelioma Progression via the MDM2-p53-Signaling Axis.
Anand. Singh (2019)
Expert Consensus on the Detection and Screening of Oral Cancer and Precancer.
Shou Yen Kao (2015)
MicroRNAs; Past, Present and the Future
Kambiz Banihashemi (2019)See more